Cited by 283Estrogen and related hormone effectsGenomics and Chromatin DynamicsStress Responses and Cortisol

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Glucocorticoid Receptor Binding to a Specific DNA Sequence Is Required for Hormone-Dependent Repression of Pro-Opiomelanocortin Gene Transcription

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Drouin, Jacques, Trifiro, Mark A., Plante, Richard K., Nemer, Mona, Eriksson, Per, Wrange, Örjan·1989·Molecular and Cellular Biology

DOI 10.1128/mcb.9.12.5305-5314.1989PMC PMC363695

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Abstract

Glucocorticoids rapidly and specifically inhibit transcription of the pro-opiomelanocortin (POMC) gene in the anterior pituitary, thus offering a model for studying negative control of transcription in mammals. We have defined an element within the rat POMC gene 5'-flanking region that is required for glucocorticoid inhibition of POMC gene transcription in POMC-expressing pituitary tumor cells (AtT-20). This element contains an in vitro binding site for purified glucocorticoid receptor. Site-directed mutagenesis revealed that binding of the receptor to this site located at position base pair -63 is essential for glucocorticoid repression of transcription. Although related to the well-defined glucocorticoid response element (GRE) found in glucocorticoid-inducible genes, the DNA sequence of the POMC negative glucocorticoid response element (nGRE) differs significantly from the GRE consensus; this sequence divergence may result in different receptor-DNA interactions and may account at least in part for the opposite transcriptional properties of these elements. Hormone-dependent repression of POMC gene transcription may be due to binding of the receptor over a positive regulatory element of the promoter. Thus, repression may result from mutually exclusive binding of two DNA-binding proteins to overlapping DNA sequences.

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Authors: Drouin, J., Trifiro, M. A., Plante, R. K., Nemer, M., Eriksson, P., & Wrange, Ö.
Affiliations: Montreal Clinical Research Institute (CA)
Karolinska Institutet (SE)
Department of Molecular Genetics, Karolinska Institutet
ORCID: Drouin, Jacques
Trifiro, Mark A.
Plante, Richard K.
Nemer, Mona
Eriksson, Per
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 1989-12
Volume: 9
Issue: 12
Pages: 5305-5314
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.9.12.5305-5314.1989
PMC: PMC363695
OpenAlex: W2161628453
Cited by: 283
References: 71
Citations by year: 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 2
FWCI: 12.99
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: glucocorticoid receptor, transcriptional repression, glucocorticoid response element, anterior pituitary, AtT-20 cells, sequence divergence
MeSH terms: Animals, Base Sequence, DNA, Genes, Molecular Sequence Data, Nucleotide Mapping, Pituitary Gland, Anterior, Plasmids, Pro-Opiomelanocortin, Protein Binding, Receptors, Glucocorticoid, Suppression, Genetic, Transcription, Genetic, Restriction Mapping, Rats

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Glucocorticoid Receptor Binding to a Specific DNA Sequence Is Required for Hormone-Dependent Repression of Pro-Opiomelanocortin Gene Transcription

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